Copper metabolism in the brain is far from being completely understood and further studies are needed on the role of copper in the CNS, starting with careful measurements, metal and biological speciation of metabolites on the molecular level, and combining copper concentration in different brain areas with morphological as well as biochemical alteration after Cu-depletion/deficiency. So far a pathological role for copper has been clearly demonstrated in some human genetic diseases (e.g., Menkes' and Wilson's diseases), but other pathological features connected with metal depletion are under investigation in several laboratories. The metabolic interaction between copper and other metal ions in some neurological disorders is also discussed in this contribution.